This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The proposed research project will focus on three different polymorphisms in dopamine-related genes which alter the amount of available CNS dopamine. Subjects will initially be screened for TMS eligibility, and then for these dopamine-related polymorphisms. Subjects falling into the desired genotype groups will be invited to participate further. These subjects will participate in two randomized conditions, one in which the subject receives levodopa prior to motor skill training and one with a placebo. It is hypothesized that neurophysiological and behavioral measures that improve with experience-dependent activity will further improve when examined in the setting of increased CNS dopamine levels;and that this enhancement will vary in relation to dopamine receptor genotype. Studies with animals, healthy humans and patients provide evidence that these genes and polymorphisms are reasonably associated with the cortical plasticity being studied here, and therefore are good candidates for evaluating genetic influences. Dependent variables will be transcranial magnetic stimulation (TMS) measures of cortical plasticity and behavioral measures of learning, as characterized by time to completion and errors on a marble navigation task.
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